This research concerns daily biological clocks, which are an important component of the physiology of humans and other organisms. For example, medical and psychiatric studies have shown that these biological clocks are involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia. Therefore, understanding the biochemical mechanism of these clocks may lead to procedures which will be useful in the diagnosis and treatment of disorders which are relevant to sleep, mental health, and pharmacology. Despite the importance of clocked phenomena, however, the nature of the underlying biochemical mechanism is unknown. The research strategy is to study the molecular and genetic nature of biological clocks in two model organisms: one prokaryotic, and the other eukaryotic. The immediate aims of his research are (I) to manipulate genetically the model organisms so that they express rhythms which can be easily screened, (2) to identify and clone genes which are involved in the timing mechanism, (3) to characterize the input pathway (light) by which this clock is synchronized to environmental time, and (4) to track the output pathways of the clock "upstream" to discover the clock mechanism itself. The long-term research goal is to understand the mechanism of this fascinating clockwork.